L1 Gene Methylation in High-Risk Human Papillomaviruses for the Prognosis of Cervical Intraepithelial Neoplasia

Oka, Noriko; Kajita, Masatoshi; Nishimura, Ryuichiro; Ohbayashi, Chiho; Sudo, Tamotsu

doi:10.1097/igc.0b013e31827da1f6

Cited by 20 publications

(17 citation statements)

References 18 publications

(24 reference statements)

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“…[19–21] HPV L1 gene was the coding gene of major capsid protein, it was found that a high level of L1 gene methylation should mean the integration status of HPV genome and host cell genome, the low level of L1 gene methylation proved that HPV genome was in free status from the host cell genome. [8] Bryant et al [22] reported that a consistent trend was existed between HPV L1 gene methylation and cell morphology changes, it could be used as a molecular target of cervical lesions’ diagnosis and treatment. So, L1 gene methylation level not only represented the status of HPV infection in cervical exfoliated cells, but also had a good correction with the cervical cell lesion.…”

Section: Discussionmentioning

confidence: 99%

“…[4–7] The L1 protein as the main capsid protein of HPV played an important role to recognize the host cell and keep persistent infection, which was a good index to evaluate the infection state in host cell. [8] Previous studies showed that the quantity of L1 protein was declining with aggravate of cervical cell lesion, L1 gene was the coding gene of L1 protein, its methylation was the major reason of L1 protein decreasing, which showed positive correlation to the degree of cervical lesions. [9,10] So, L1 gene methylation deeply involved in the progression and heterogeneity of cervical lesions, which was the potential clinical molecular target of cervical lesions to early diagnose and monitor the prognosis.…”

Section: Introductionmentioning

confidence: 99%

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Increased HPV L1 gene methylation and multiple infection status lead to the difference of cervical epithelial cell lesion in different ethnic women of Xinjiang, China

et al. 2017

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Human papillomavirus (HPV) L1 gene methylation deeply involved in the progression and heterogeneity of cervical cell epithelial lesions. The DNA ploidy also represented the early lesions of cervical cell, and it was associated with different HPV infection status in different ethnic women. So, the research was to explore whether it was possible that HPV L1 gene methylation and HPV infection status as the risk factors to lead to the differences of cervical epithelial cells’ lesions in different ethnics women.The flow-through hybridization and gene chip for HPV genotypes test, general characteristics, and cervical exfoliated cell samples were collected from 94 Uygur and 79 Han women with HPV-16 infection. The cases were divided into the single HPV-16 (sHPV-16) infection group and multiple HPV-16 (mHPV-16) infection group in each ethnic women. The DNA ploidy was analyzed by flow cytometry, and the methylation-sensitive high resolution melting (MS-HRM) was used to test the HPV-16 L1 gene methylation, the results of methylation was segmented into mild methylation, moderate methylation, and severe methylation groups. Multifactor logistic analysis explored the relation between DNA heteroploid and HPV-16 infection status, HPV-16 L1 gene methylation in different ethnic women.The higher proportion of mHPV-16 infection in Uygur than Han women (61.7% vs 38.0%). L1 gene methylation had statistic difference between single and mHPV-16 infection under the same ethnic women. The proportion of DNA heteroploid had statistic difference between different HPV-16 infection status or different L1 gene methylation grades in Han or Uygur women. Both L1 gene methylation and HPV infection status were the risk factors of DNA heteroploid. Compared to the sHPV-16 infection, the odds ratio (OR) of mHPV-16 infection were 4.409 (CI: 1.398–13.910) and 3.279 (CI: 1.069–10.060) in Han and Uygur women. Compared the mild L1 gene methylation, the OR of moderate L1 gene methylation were 3.313 (CI: 1.002–10.952) and 5.075 (CI: 1.385–18.603) in Han and Uygur women, the OR of severe L1 gene methylation were 20.592 (CI: 3.691–114.880) and 63.634 (CI: 10.400–389.368) in Han and Uygur women.The study first reported that HPV L1 gene methylation and HPV infection status were the risk factors to the DNA heteroploid of cervical cell in different ethnics women, HPV L1 gene methylation and infection status should be recommended to the existing system of cervical lesion screening in order to provide better serves for the HPV infected women, especially for the ethnic women with high proportion of severe L1 gene methylation and multiple infection status.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Increased HPV L1 gene methylation and multiple infection status lead to the difference of cervical epithelial cell lesion in different ethnic women of Xinjiang, China

et al. 2017

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“…Quantification of these changes may contribute to the diagnosis and prognostication of cervical cancer [15] . The L1 gene of HPV is preferentially methylated in cellular DNA, and this methylation is correlated with cervical precancerous progression, which may be used as a marker for detecting the grade and progression of neoplasia [16,17] .…”

mentioning

confidence: 99%

Correlation between Methylation of Human Papillomavirus-16 L1 Gene and Cervical Carcinoma in Uyghur Women

Niyazi

Sui²,

Zhu³

et al. 2016

Gynecol Obstet Invest

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Background: This study aims at determining the correlation between CpG methylation in human papillomavirus (HPV)-16 L1 and the persistent infections and development of cervical carcinoma in Uyghur women. Methods: Among the 4,364 Uyghur women, specimens were collected from 145 (3.3%) HPV-16 single infected cases, which were divided into 5 groups: transient infection (n = 32), persistent infection (n = 21, 12 months), cervical intraepithelial neoplasia (CIN) grade 1 (CIN1, n = 21), CIN2-3 (n = 33) and invasive cervical cancer (n = 38) groups. Methylation level in HPV-16 L1 was quantified by pyrosequencing, and values in the prediction and diagnosis of CIN2+ lesions were evaluated with receiver operating characteristic curves. Results: With the progression of the disease, increased methylation was detected at 13 CpG sites, and a high methylation level was associated with the risk of CIN2+. The strongest related site was 6650 (OR 9.89, 95% CI 3.57-27.44). The area under ROC curve (AUC) of methylation at each CpG site to differentiate between CIN2+ and

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“…In addition, previous studies examining the epigenetic property of HPV-16 suggest that the L1 gene presents higher methylation levels in high-grade cervical lesions compared to asymptomatic infection or low-grade lesions [26,27], similar with our study. Oka et al reported that high methylation levels indicate the DNA integration linking to the progression of disease, whereas low methylation levels indicate an episomal HPV genome status in host cells [28]. These findings demonstrate that L1 gene methylation may be a consequence of HPV genomic integration [29].…”

Section: Discussionmentioning

confidence: 91%

High-resolution melting analysis of HPV-16L1 gene methylation: A promising method for prognosing cervical cancer

Qiu

Zhi

Shen

et al. 2015

Clinical Biochemistry

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L1 Gene Methylation in High-Risk Human Papillomaviruses for the Prognosis of Cervical Intraepithelial Neoplasia

Cited by 20 publications

References 18 publications

Increased HPV L1 gene methylation and multiple infection status lead to the difference of cervical epithelial cell lesion in different ethnic women of Xinjiang, China

Increased HPV L1 gene methylation and multiple infection status lead to the difference of cervical epithelial cell lesion in different ethnic women of Xinjiang, China

Correlation between Methylation of Human Papillomavirus-16 L1 Gene and Cervical Carcinoma in Uyghur Women

High-resolution melting analysis of HPV-16L1 gene methylation: A promising method for prognosing cervical cancer

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